DESCRIPTION (applicant's abstract): Corticotropin-releasing factor (CRF) is known to be a major regulator in response to stress. The recent cloning and characterization of urocortin (UCN), a CRF-like peptide, has opened a new direction in the study of the function of the CRF peptide family in the brain. Most of the UCN-producing neurons are found in the Edinger-Westphal nucleus (EW) in the midbrain region, with some scattered UCN neurons found in the forebrain and brainstem regions. Central administration of UCN has been shown to exhibit a potent appetite suppressing effect. However, the mechanism by which UCN neurons modulate appetite is not clear. In the proposed project, neuroanatomical studies will first be performed to determine the potential targets for UCN in the brain and to identify the origin of the UCN neurons that provided the UCN input. Secondly, the function of UCN in its target areas will be assessed. Finally, the hypothesis that endogenous UCN neurons are involved in appetite regulation will be further tested to examine whether UCN gene expression in the brain can be altered by changing metabolic condition or by important peripheral metabolic signals such as leptin.